Model of BDV-induced neurodevelopmental damage of hippocampal cells by altered neuronal connectivity of granule cells.

In contrast to many other viruses, Borna Disease Virus (BDV)-infected cells, including primary neurons, are not impaired in their viability. BDV is therefore regarded as a non-cytolytic virus that causes a persistent infection of the central nervous system. However, in the hippocampus of BDV-infected newborn Lewis rats, a subset of neurons, the dentate granule cells (DGCs), undergo progressive cell death. The events that lead to the neuronal death of these cells are unknown, especially since detailed studies were hampered by the lack of an accessible model system. Using organotypic hippocampal slice cultures of newborn rat pups, we succeeded in establishing an ex vivo model system to study this virus-induced neuronal damage. With this system we could show that BDV induces disturbances in the synaptic organization, axon retraction and subsequent death of DGCs. Our goal is to unveil the molecular mechanisms that lead to this neuronal damage and hope to gain fundamental insights into the process of virus-induced neuronal degeneration and synaptic changes.

Additional information: http://www.ukl.uni-freiburg.de/microbio
contact person: Prof.Dr. Martin Schwemmle
Phone: 0761 203-6526
Email: martin.schwemmle@uniklinik-freiburg.de

Start of project: 2004
End of project: (unlimited)

Albert-Ludwigs-University Freiburg
Schwemmle, Martin
Department für Medizinische Mikrobiologie und Hygiene
Institut für Virologie
Hermann-Herder-Strasse 11
79104 Freiburg
Germany

Phone: +49 761 203 6534
Fax: +49 761 203 6626
http://www.virologie.uniklinik-freiburg.de
Actual Research Report

• Gonzalez-Dunia D, Volmer R, Mayer D, Schwemmle M: Borna disease virus interference with neuronal plasticity Virus Res, 2005; 111: 224-234.
• Schwemmle M, Lipkin WI: Models and mechanisms of Bornavirus pathogenesis. Drug Discov Today, 2004; 2: 211-216.